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Biomedical subjects

H M Jansen

Publications and source records attributed to H M Jansen.

At least 145 records · Page 8Linked to original sources

Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence.

To analyze whether exacerbations in chronic obstructive pulmonary disease (COPD) coincide with reinfection by Haemophilus influenzae, 16 COPD patients were studied longitudinally for 3 years. Exacerbations coincided with reinfection by H. influenzae, either endogenous, by a strain with a DNA fingerprint indistinguishable from the strain previously present but with another major outer membrane protein (MOMP) pattern (2 patients), or exogenous, by a strain with a different DNA fingerprint and MOMP pattern (3 patients). The other patients, remaining in an infectious state without clear exacerbations for longer periods, were persistently infected by a particular H. influenzae strain (median persistence time, 5.5 months; range, 2-23 months). Of 8 antibiotic-treated patients, 7 remained infected by H. influenzae with the same DNA fingerprint, although all strains were sensitive to the antibiotics prescribed. Results of the study suggested that exacerbations in COPD patients coincide with endogenous or exogenous reinfection by H. influenzae, persistently infected patients keep the same H. influenzae strain for longer periods, and antibiotic treatment was not effective in eradicating H. influenzae.

Adult↗

Antigens in culture supernatant of Mycobacterium tuberculosis: epitopes defined by monoclonal and human antibodies.

Antigens of Mycobacterium tuberculosis found in the supernatant of heat-treated cultures were characterized in order to explore whether antigens from this source could be used for the development of a serological test. Culture supernatants and sonicates of 12, 25 and 39 d cultures were analysed by SDS-PAGE. In culture supernatant, major protein bands of 65, 24, and 12 kDa were visible after Coomassie brilliant blue staining. Using murine monoclonal antibodies in Western blots, a pattern of protein bands distinct from that of the corresponding M. tuberculosis sonicates was found in all the culture supernatants. Gel permeation chromatography, in the presence of SDS, was used to separate the major protein bands in the culture supernatant. In ELISA, sera from 20 of 26 patients with tuberculosis reacted with fractions containing mainly 24 kDa or 12 kDa proteins, whereas none of the control sera reacted. In Western blots, each patient serum had its own characteristic banding pattern with culture supernatant, but all the sera from tuberculosis patients and control subjects reacted with protein bands of 65, 61, 58, 30 and 24 kDa. The 12 kDa protein was recognized only by sera from patients with tuberculosis in both Western blots and ELISA. This suggests that different kinds of epitopes on proteins of M. tuberculosis are detected by human antibodies in Western blots and ELISA. We assume that epitopes recognized in Western blots by patients with tuberculosis and control subjects are ubiquitous and are also present on normal commensal bacteria. Epitopes recognized by only some patients with tuberculosis in Western blots may be linear and M. tuberculosis specific. Epitopes recognized by tuberculosis patients but by none of the control subjects in ELISA may be conformation related and M. tuberculosis specific. The major protein bands found in supernatants of heat-treated cultures, 24 and 12 kDa, possess epitopes that may be M. tuberculosis specific and are potentially valuable for the development of a serological test.

Antibodies, Bacterial↗

Lung function 8-18 years after intermittent positive pressure ventilation for hyaline membrane disease.

Lung function and respiratory symptoms were studied in 40 children aged 8-18 years who had been ventilated for hyaline membrane disease after birth; 11 had had bronchopulmonary dysplasia. Also studied were 38 age matched children who had had hyaline membrane disease but had not required ventilation, 25 unmatched children who were born prematurely but did not develop hyaline membrane disease, and 39 randomly selected pupils of similar age. There was no difference in thoracic gas volume, total lung capacity, inspiratory vital capacity, residual volume, or transfer factor for carbon monoxide between the groups. Respiratory symptoms during the three years before the study and the frequency of clinically diagnosed asthma in patients and their family were similar in all the children with hyaline membrane disease irrespective of whether they had been ventilated or had had bronchopulmonary dysplasia. The children with bronchopulmonary dysplasia, however, had a lower forced expiratory volume in one second (FEV1) before bronchodilator (73% predicted) than the other groups (88-95% predicted). Children who had required ventilation had lower values for specific airways conductance (sGaw) and a greater increase in FEV1 (delta FEV1) after salbutamol (13%) than non-ventilated children (6%); delta FEV1 was associated with the peak pressure of intermittent positive pressure ventilation, a family history of asthma and a history of wheezing, recurrent respiratory illnesses, and a doctor's diagnosis of asthma during the three years before the study. These findings indicate that after eight years of age patients with bronchopulmonary dysplasia have more reversible airways obstruction, compatible with increased bronchial smooth muscle tone.

Adolescent↗

Haemophilus influenzae infections in patients with chronic obstructive pulmonary disease despite specific antibodies in serum and sputum.

The titer and specificity of antibodies to the infecting Haemophilus influenzae was determined in sera and sputa from 27 patients with chronic obstructive pulmonary disease (COPD) to analyze the specific immune response. COPD patients had significantly higher serum IgG and IgA antibody titers than 13 healthy controls (mean IgG titers 12,302 and 5,623, respectively; mean IgA titers, 2,398 and 912; p less than 0.001). The mean IgM titers were comparable: 501 and 447, respectively. Specific IgA antibodies were also detectable in the sputum of the COPD patients (mean IgA antibody titer, 776). The local antibody production was determined by calculating the relative coefficient of excretion (RCE) to albumin. The mean RCE of 89.1 for IgA indicated statistically significant local production (p less than 0.02), in contrast to a nonsignificant increase for IgG (mean RCE of 3.6). Specific IgM was below the detection level. Immunoblotting experiments showed that the antibodies in sera from COPD patients and controls were directed against most of the outer membrane proteins of H. influenzae, with individual differences between IgG, IgA, and IgM. The IgA and IgG antibodies in serum had a similar specificity as those in sputum. The appearance or persistence of H. influenzae coincided with minor changes in antibody titer and specificity. From these results we conclude that COPD patients are infected with H. influenzae despite the presence of at least as many antibodies in sputum and serum as in controls and that these antibodies are directed against a variety of antigenic determinants of the infecting strain.

Adult↗

[AIDS and tuberculosis; a retrospective study in 225 patients with AIDS].

Of 225 patients in whom AIDS was diagnosed in the period January 1982 to March 1988 at the Academic Medical Centre, Amsterdam, the tuberculosis incidence and the clinical and demographic characteristics were recorded retrospectively. Tuberculosis was diagnosed in 18 patients (8%). The most frequent risk factor of AIDS-tuberculosis patients was intravenous drug abuse. The chest X-ray was frequently atypical and there were more extrapulmonary locations in comparison to patients with tuberculosis without AIDS. On September 1, 1988, 13 of the 18 patients had died. The response to tuberculostatic therapy was good. Our results are in agreement with comparable studies elsewhere. The expectation is that the tuberculosis incidence among AIDS patients will increase as more intravenous drug users become part of the whole AIDS patient population.

Acquired Immunodeficiency Syndrome↗

Antigenic drift of Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

Differences in the major outer membrane protein b,c (molecular weight, 39,000 to 41,000) of related Haemophilus influenzae strains isolated from the sputum of patients with chronic obstructive pulmonary disease were analyzed biochemically and immunologically. Protein b,c was isolated from a total of six related H. influenzae strains from two chronic obstructive pulmonary disease patients. After CNBr digestion of the proteins, the differences in size appeared in the larger of the two fragments. Trypsin and chymotrypsin digests of proteins from related H. influenzae strains showed that proteins differed by only a few peptides or were very similar, in contrast to the peptide maps of proteins from nonrelated strains. Peptide analysis of b,c proteins from related H. influenzae strains by high-performance liquid chromatography after Staphylococcus aureus V8 protease digestion and amino acid analysis of corresponding fractions revealed highly comparable patterns, indicating only minor differences in the amino acid sequences of these proteins. Immunization of rabbits with intact bacteria of four related H. influenzae strains resulted in a strong anti-protein b,c antibody response in all animals. In three of four rabbits, antibodies specific for the b,c protein of the strain used for immunization were elicited, indicating that the changed proteins contained specific immunodominant epitopes. Anti-protein b,c antibodies promoted strain-specific, complement-dependent, bactericidal activity. From these results, we conclude that H. influenzae shows antigenic drift in immunodominant epitopes, caused by small changes in amino acid composition of the b,c protein. Antibodies to these epitopes promote complement-dependent bactericidal activity.

Animals↗

Renal handling of indomethacin: isolated membrane vesicles of proximal tubular cells as an in vitro model system for transport.

The indomethacin-transport properties of luminal and contraluminal membrane vesicles derived from dog renal proximal tubular cells were studied. In both membranes saturable sodium gradient-dependent transport of indomethacin, sensitive to probenecid, was observed. In luminal membrane vesicles uptake occurred predominantly by passive facilitated diffusion, whereas in contraluminal membrane vesicles, uptake was based upon both passive simple diffusion and active concentrative transport. As a result, indomethacin may accumulate in vivo in the tubular cells thereby exerting a direct nephrotoxic effect.

Animals↗

Skin tests and histamine release with P1-depleted Dermatophagoides pteronyssinus body extracts and purified P1.

Monoclonal antibodies were raised against P1 and Dp X, two major allergens in Dermatophagoides pteronyssinus extracts. The concentrations of IgE antibodies to P1 and Dp X in sera of mite-sensitive patients were determined in RAST with immunosorbent-bound monoclonal antibodies used for insolubilization of the allergens. The major allergen-specific IgE titers were compared with the total IgE response against D. pteronyssinus. The results of these serologic assays confirmed studies in the literature that P1 and Dp X are major allergens. The contribution of IgE anti-P1 to the total antimite response frequently exceeded 50% and, in general, appeared to be higher than the contribution of IgE anti-Dp X. Twenty percent of the mite-sensitive patients had no detectable IgE to either P1 or Dp X. The contribution of P1 to the biologic activity of D. pteronyssinus body extracts was derived from the effect of P1 depletion on the reactivity in the histamine-release test and skin test. This technique was preferred to the study of purified allergen because biologic activity of the nonabsorbed components is not affected. Immunization of rabbits with affinity-purified P1 yielded monospecific polyclonal antisera. Mite extracts depleted with either monoclonal or polyclonal anti-P1 were applied in the histamine-release test. The skin test was performed with extracts depleted with polyclonal anti-P1. In addition, the activity of affinity-purified P1 was investigated in these tests. The results indicated that P1 depletion of D. pteronyssinus body extracts had no detectable effect on the activity in most patients, namely, at least 70% of the activity was retained in the depleted extract. There was a considerable variation between patients in the sensitivity for purified P1, as compared to the sensitivity for whole D. pteronyssinus extracts. In the histamine-release test, the activity of purified P1 was up to 35% of the activity of the D. pteronyssinus body extract but did not exceed 10% in most patients. This was in agreement with the relative activity of purified P1, as found in the skin test. Therefore, the contribution of P1 to the biologic activity of D. pteronyssinus body extracts, as measured by end point titration, appeared to be less than expected on the basis of the serologic studies and articles in literature. The depletion experiments stress that there is still much uncertainty as to the biologic activity of house dust-mite extracts.

Adolescent↗

Discrepancies between the skin test and IgE antibody assays: study of histamine release, complement activation in vitro, and occurrence of allergen-specific IgG.

Intracutaneous skin tests (STs) and RAST with the common allergens, grass pollen, house dust mite, and cat dander, were performed on 660 adult patients. In 117 patients (18%), we found 140 discordances (7%) in a total number of 1980 ST and RAST combinations. In agreement with studies in the literature, greater than 80% of the discordances consisted of positive skin reactions without detectable allergen-specific IgE antibodies in serum. The percentages of discordant results were similar for the three allergens. Reproducibility of both the RAST and the ST was evaluated in the discordant group. Repetition of the routine RAST procedure elicited results similar to those in the first test in 81% (105/130). A second ST elicited identical results in 89% (47/53). In addition to the routine IgE antibody assay, sera of patients with a positive ST but without detectable IgE antibodies were tested in two other RAST systems: (1) a RAST with allergen extracts from the same production batch as the ST reagents, and (2) the Pharmacia RAST. In spite of having a clearly positive ST, sera from 68 (80%) of 85 patients remained completely negative in all three RAST systems. Histamine release (HR) in vitro from washed leukocytes was studied in 35 patients with a reproducible positive ST and negative RAST results with serum. Interpretation of this test was possible in 28 patients. In 82% (23/28) of these patients, clearly detectable HR was found with the relevant allergen extract. A role of IgE in the skin reactions and HR tests was confirmed by positive RAST results with IgE that was affinity purified from serum of seven of these patients. Allergen-specific IgG4 antibodies are unlikely to be implicated, since no antibodies against grass pollen and house dust mite were detectable in sera of these patients. Only 18% of the patients with an unexplained skin reaction with cat dander have detectable IgG4 antibodies, but these antibodies were found in a similar frequency in a nonallergic, ST negative control group. Low total IgG responses precluded false negative RAST results caused by competition of IgG antibodies with IgE antibodies. There were no significant differences in the degree of complement activation in vitro by house-dust extracts between healthy control subjects, nonallergic patients, and patients with unexplained skin reactivity. It is concluded that a high proportion of the positive skin reactions with common inhalant allergens, which are not accompanied by a positive RAST, are probably caused by IgE antibodies that are not detectable in serum with any of the RAST procedures.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Lung volume calculations from 81Krm SPECT for the quantification of regional ventilation.

Lung volumes, calculated from 81Krm single-photon emission computed tomography (SPECT) of the lungs, were compared with functional residual capacity (FRC), measured with the helium dilution technique in controls and in patients with various pulmonary diseases. SPECT volume was greater than FRC, which was attributed to non-gas-containing structures in the lung such as the alveolar walls, the interstitium, the blood vessels and the blood, included in the SPECT volume. A good correlation (r = 0.91) was found between the two volumes and there was no difference in this relationship between patients and controls. It was concluded that the relative volume distribution, calculated from SPECT, can be used for the quantification of ventilation from 81Krm SPECT steady-state count distributions.

Adult↗

Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

Five individual colonies of Haemophilus influenzae were isolated from each of one to three cultures of sputum collected from 18 patients with chronic obstructive pulmonary disease (COPD). The isolates were studied to investigate whether the major outer membrane proteins (MOMPs) changed during persistence. The relationship between isolates was analyzed by fingerprinting their chromosomal DNA. The fingerprints of eight strains (isolated from eight patients) with various MOMP compositions were different, whereas fingerprints of isolates with identical MOMP compositions were indistinguishable. In 12 patients, two or more strains with different MOMP compositions were found; one strain was isolated from the sputum samples of each of the six remaining patients. In seven of the 12 patients, strains with different MOMPs but with indistinguishable fingerprints were found. The differences were found in proteins b,c (five patients) and d (five patients). In patients with COPD, the MOMPs of H. influenzae are subject to changes that may enable this bacterium to escape immunological defense mechanisms.

Bacterial Outer Membrane Proteins↗

ELISA of ceruloplasmin and alpha-2-macroglobulin in paired bronchoalveolar lavage fluid and serum samples.

Bronchoalveolar lavage fluid (BALF) was analysed to obtain information on leakage of proteins from the blood into the respiratory lumen and on local synthesis. Albumin, ceruloplasmin and alpha-2-macroglobulin were measured in paired BALF and serum samples from patients with acute pneumonitis or asthma. Ceruloplasmin (CP) and alpha-2-macroglobulin (A2M) were measured by ELISAs thereby avoiding concentration of BALF. The quotients 10(3) ([protein]BALF)/(protein]serum), Qprotein, were calculated as well as the relative coefficients of excretion, RCE: Qprotein/Qalbumin. The QCP and QA2M increased parallel to Qalbumin in patients with pneumonitis and QCP increased parallel with Qalbumin in the asthma patients. This indicates that abnormal leakage of proteins from the blood rather than local synthesis cause the increased concentrations of these proteins in the BALF. Increased values for the RCE of CP and A2M were observed at normal Qalbumin. We therefore conclude that the determination of CP and A2M yields more detailed information on leakage of proteins from the blood into the airway compartment than that of albumin.

Adolescent↗

Whole-lung lavage under hyperbaric oxygen conditions for alveolar proteinosis with respiratory failure.

Whole-lung lavage under hyperbaric oxygen conditions was performed in two patients suffering from severe respiratory insufficiency in pulmonary alveolar proteinosis. Under these conditions, gas exchange was maintained and the mixed venous partial pressure of oxygen and oxygen saturation showed increases to acceptable levels. This enabled us to limit the FIO2 in order to extend the oxygen tolerance and to perform lavage procedures more effectively. Both patients showed a very significant improvement of their clinical course, and we conclude that elective use of hyperbaric oxygen in unilateral lung lavages should be considered in these severe cases.

Adult↗

Distribution of ventilation-perfusion ratios in pulmonary sarcoidosis.

In 14 patients with advanced stage pulmonary sarcoidosis the distribution of regional ventilation-perfusion ratios (V/Q) was obtained by quantitative analysis of ventilation-perfusion single photon emission computed tomography (SPECT) of the lungs. In 6 patients normal V/Q distributions were found with a decreased DLCO in only one of them. In 8 patients abnormal distributions of V/Q ratios were found. Six of these patients also had a decrease in diffusing capacity for CO (DLCO). It is suggested that the decrease in DLCO in these patients is partly a result of uneven distribution of V/Q ratios.

Adult↗